engleski

THE EFFECTS OF AT1 RECEPTOR ANTAGONISM ON ENDOTHELIAL FUNCTION, AND ENDOTHELIAL CELL ADHESION MOLECULES AND THEIR LIGANDS EXPRESSION IN HYPERTENSIVE PATIENTS

urpose: To determine the effects of AT1 receptor antagonism on endothelial function, soluble endothelial cell adhesion mo- lecules and their ligands expression on circulatory leukocyte in hypertensive patients. Methods: Newly discovered hypertensive subjects of both sexes (N=30 ; age: 53±8.1 yrs) were treated with AT1 antagonist, olme- sartan (10-20mg/day for 8 weeks ; to reach BP≤139/89mmHg). Flow-mediated dilation (FMD) of brachial artery (BA) was asse- ssed by ultrasound (Acuson Siemens X300 ; ultrasound probe VF10-5 ; 105 MHz), the serum sCAMs were determined by ELISA kits and level of sCAMs ligands on leukocytes was asse- ssed by flow cytometry before and after 8 weeks of treatment. The BA diameter, relative change in the diameter (delta D) and percentage of diameter change (FMD%) were calculated for pre- occlusion, and after duration of occlusion for 1, 2 and 3 minutes. Paired t-test, or t-test were used as appropriate, with Pearson’s correlation calculated. Data are expressed as mean±SD ; p<0.05 was significant (SigmaPlot v.11).The study was approved by Ethical Committees of our institutions. All patients volunteered in the study. Results: Arterial blood pressure (BP) significantly decreased with AT1 antagonist. The BA diameter was signifi- cantly wider at pre-occlusion and after each occlusion irrespec- tively of its duration, while delta D and FMD% were significantly reduced with olmesartan. sICAM-1 and sVCAM-1 levels signi- ficantly decreased, whereas E-selectin levels significantly increa- sed with BP reduction. Before therapy, CD11a and CD49d were dominantly expressed on monocytes, whereas CD15 was almost exclusively expressed on granulocytes. Lymphocytes expressed intermediate levels of CD11a and CD49d ligands compared to other cell types. Except of CD11a on monocytes which increased significantly, the expression of other leukocyte ligands remained stable after therapy. sICAM-1 positively correlated with systolic BP and sVCAM-1 with systolic and diastolic BP. sE-selectin in- versely correlated with the reduction of both systolic and diasto- lic BP. Conclusions: Due to decrease in BP, blood vessels relaxed, thus making FMD response less vigorous. Decrease of sICAM-1 (and VCAM-1) together with the increased expression of mo- nocytes’ CD11a suggests the de-activation of endothelium with reduction in BP, possibly decreasing the adherence of circulatory leukocytes to endothelium ; subsequently lessening the risk for development of atherosclerotic lesions.

AT-1 receptors; cell adhesion molecules; flow-mediated dilation

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